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different roles of n-terminal and c-terminal domains in calmodulin for activation of bacillus anthracis edema factor.bacillus anthracis adenylyl cyclase toxin edema factor (ef) is one component of the anthrax toxin and is essential for establishing anthrax disease. ef activation by the eukaryotic ca2+-sensor calmodulin (cam) leads to massive camp production resulting in edema. camp also inhibits the nicotinamide adenine dinucleotide phosphate (nadph)-oxidase, thus reducing production of reactive oxygen species (ros) used for host defense in activated neutrophils and thereby facilitating bacterial growth. methi ...201526184312
effects of 39 compounds on calmodulin-regulated adenylyl cyclases ac1 and bacillus anthracis edema factor.adenylyl cyclases (acs) catalyze the conversion of atp into the second messenger camp. membranous ac1 (ac1) is involved in processes of memory and learning and in muscle pain. the ac toxin edema factor (ef) of bacillus anthracis is involved in the development of anthrax. both acs are stimulated by the eukaryotic ca(2+)-sensor calmodulin (cam). the cam-ac interaction could constitute a potential target to enhance or impair the ac activity of ac1 and ef to intervene in above (patho)physiological m ...201525946093
[screening and antibacterial function of bacillus amyloliquefaciens x030].we isolated 339 bacillus strains from 72 soil samples all over the country, then purified their antimicrobial compounds and studied the antibacterial activity, to enrich bacillus resources and explore their second metabolites.201526762026
spore germination.despite being resistant to a variety of environmental insults, the bacterial endospore can sense the presence of small molecules and respond by germinating, losing the specialized structures of the dormant spore, and resuming active metabolism, before outgrowing into vegetative cells. our current level of understanding of the spore germination process in bacilli and clostridia is reviewed, with particular emphasis on the germinant receptors characterized in bacillus subtilis, bacillus cereus, an ...201527337279
lack of evidence for plague or anthrax on the new york city subway.ackelsberg et al. point out a lack of evidence in the dataset of afshinekoo et al. for the presence of plague and anthrax on the new york city subway.201527135683
a d-amino acid at the n-terminus of a protein abrogates its degradation by the n-end rule pathway.eukaryotes have evolved the ubiquitin (ub)/proteasome system to degrade polypeptides. the ub/proteasome system is one way that cells regulate cytosolic protein and amino acids levels through the recognition and ubiquitination of a protein's n-terminus via e1, e2, and e3 enzymes. the process by which the n-terminus stimulates intracellular protein degradation is referred to as the n-end rule. characterization of the n-end rule has been limited to only the natural l-amino acids. using a cytosolic ...201526807441
whole genome analysis of injectional anthrax identifies two disease clusters spanning more than 13 years.anthrax is a rare disease in humans but elicits great public fear because of its past use as an agent of bioterrorism. injectional anthrax has been occurring sporadically for more than ten years in heroin consumers across multiple european countries and this outbreak has been difficult to trace back to a source.201526870786
composite sampling approaches for bacillus anthracis surrogate extracted from soil.any release of anthrax spores in the u.s. would require action to decontaminate the site and restore its use and operations as rapidly as possible. the remediation activity would require environmental sampling, both initially to determine the extent of contamination (hazard mapping) and post-decon to determine that the site is free of contamination (clearance sampling). whether the spore contamination is within a building or outdoors, collecting and analyzing what could be thousands of samples c ...201526714315
cd4+ t cells targeting dominant and cryptic epitopes from bacillus anthracis lethal factor.anthrax is an endemic infection in many countries, particularly in the developing world. the causative agent, bacillus anthracis, mediates disease through the secretion of binary exotoxins. until recently, research into adaptive immunity targeting this bacterial pathogen has largely focused on the humoral response to these toxins. there is, however, growing recognition that cellular immune responses involving ifnγ producing cd4+ t cells also contribute significantly to a protective memory respon ...201526779161
diversity, antimicrobial and antioxidant activities of culturable bacterial endophyte communities in aloe vera.twenty-nine culturable bacterial endophytes were isolated from surface-sterilized tissues (root, stem and leaf) of aloe vera and molecularly characterized to 13 genera: pseudomonas, bacillus, enterobacter, pantoea, chryseobacterium, sphingobacterium, aeromonas, providencia, cedecea, klebsiella, cronobacter, macrococcus and shigella. the dominant genera include bacillus (20.7%), pseudomonas (20.7%) and enterobacter (13.8%). the crude and ethyl acetate fractions of the metabolites of six isolates, ...201526454221
[development of specific therapy to category a toxic infections].category a select agents continue to be major threat to human population both as naturally occurring diseases and as potential weapon of bioterrorists. anthrax and botulism are probably the most threatening agents as both have virtually uncontrolled natural reservoirs from which they can be isolated and propagated. available specific antitoxin therapy of both diseases is outdated; its efficiency is questionable as well as safety of reactogenic or human-derived components used in treatment. highl ...201526710525
anthrax susceptibility: human genetic polymorphisms modulating antxr2 expression.anthrax toxin causes anthrax pathogenesis and expression levels of antxr2 (anthrax toxin receptor 2) are strongly correlated with anthrax toxin susceptibility. previous studies found that antxr2 transcript abundance varies considerably in individuals of different ethnic/geographical groups, but no eqtls (expression quantitative trait loci) have been identified. by using 3c (chromatin conformation capture), crispr-mediated genomic deletion and dual-luciferase reporter assay, gene loci containing ...201526703731
does bacillus anthracis lethal toxin directly depress myocardial function? a review of clinical cases and preclinical studies.the us outbreak of b.anthracis infection in 2001 and subsequent cases in the us and europe demonstrate that anthrax is a continuing risk for the developed world. while several bacterial components contribute to the pathogenesis of b. anthracis, production of lethal toxin (lt) is strongly associated with the development of hypotension and lethality. however, the mechanisms underlying the cardiovascular instability lt produces are unclear. some evidence suggests that lt causes shock by impairing t ...201526703730
cutaneous anthrax in an unusual location: case report.cutaneous anthrax is well known, unlike anthrax of the lumbar region, which is not reported elsewhere. we present a case of anthrax of the lumbar region in a 50-year-old man. the infection was characterised by a wide, black eschar and oedema on an erythematous ground. after isolation of the gram-positive bacilli from the skin lesions, prompt antibiotic treatment (intravenous sulbactam-ampicillin 1.5 g every six hours) was initiated. following eradication of the bacilli after 14 days of antibioti ...201526700091
historical cases of anthrax in sweden 1916-1961.as in most european countries, anthrax was common in swedish livestock during the centuries leading up to the mid-twentieth century. after 1957, the disease was regarded as practically extinct. however, in the past 7 years, three outbreaks have caused public alarm because of the risk of environmental contamination. properly buried carcasses should present little risk of spore contamination, and instructions were in place to ensure this since the 1890s. however, as has been demonstrated in recent ...201526671241
spatio-temporal patterns of an anthrax outbreak in white-tailed deer, odocoileus virginanus, and associated genetic diversity of bacillus anthracis.anthrax, a soil-borne zoonosis caused by the bacterium bacillus anthracis, is enzootic in areas of north america with frequent outbreaks in west texas. despite a long history of study, pathogen transmission during natural outbreaks remains poorly understood. here we combined case-level spatio-temporal analysis and high resolution genotyping to investigate anthrax transmission dynamics. carcass locations from a single white-tailed deer, odocoileus virginanus, outbreak were analyzed for spatial cl ...201526669305
infantile systemic hyalinosis in identical twins.infantile systemic hyalinosis (ish) is a rare disorder belonging to the heterogeneous group of genetic fibromatoses. it is a rare, progressive, fatal autosomal recessive condition characterized by widespread deposition of hyaline material in many tissues caused by mutations in the anthrax toxin receptor 2 gene - antxr2. it presents hyperpigmented skin over bony prominences. characteristic purplish patches develop over the medial and lateral malleoli of the ankles, the metacarpophalangeal joints, ...201526668783
genetic characterization of bacillus anthracis 17 jb strain.bacillus anthracis is one of the most homogenous bacteria ever described. some level of diversity. bacillus anthracis 17jb is a laboratory strain it is broadly used as a challenge strain in guinea pigs for potency test of anthrax vaccine.201526668705
real-time pcr identification of unique bacillus anthracis sequences.bacillus anthracis is a spore-forming, gram-positive microorganism. it is a causative agent of anthrax, a highly infectious disease. it belongs to the "bacillus cereus group", which contains other closely related species, including bacillus cereus, bacillus thuringiensis, bacillus mycoides, bacillus weihenstephanensis, and bacillus pseudomycoides. b. anthracis naturally occurs in soil environments. the ba5345 genetic marker was used for highly specific detection of b. anthracis with taqman probe ...201526667574
[optimization of labeling and localizing bacterial membrane and nucleus with fm4-64 and hoechst dyes].to observe cell membrane and nucleus in bacteria for subcellular localization.201526665605
smallpox, anthrax, and the historiography of cutaneous diseases. 201526650656
approval of raxibacumab for the treatment of inhalation anthrax under the us food and drug administration "animal rule".on december 14, 2012, the fda approved raxibacumab, the first monoclonal antibody product developed under project bioshield to achieve this milestone, and the first biologic product to be approved through the fda animal efficacy rule (or "animal rule"). raxibacumab is approved for the treatment of adult and pediatric patients with inhalational anthrax due to bacillus anthracis in combination with appropriate antibiotic drugs and for prophylaxis of inhalational anthrax when alternative therapies ...201526648915
"in-house" production of dna size marker from a vaccinal bacillus anthracis strain.dna molecular weight marker is widely used in molecular biology experiments incurring considerable costs on low-budget settings.201526644873
observations on the inactivation efficacy of a maldi-tof ms chemical extraction method on bacillus anthracis vegetative cells and spores.a chemical (ethanol; formic acid; acetonitrile) protein extraction method for the preparation of bacterial samples for matrix assisted laser desorption ionisation time-of-flight mass spectrometry (maldi-tof ms) identification was evaluated for its ability to inactivate bacterial species. initial viability tests (with and without double filtration of the extract through 0.2 μm filters), indicated that the method could inactivate escherichia coli mre 162 and klebsiella pneumoniae atcc 35657, with ...201526633884
clinical framework and medical countermeasure use during an anthrax mass-casualty incident.in 2014, cdc published updated guidelines for the prevention and treatment of anthrax (hendricks ka, wright me, shadomy sv, et al. centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. emerg infect dis 2014;20[2]. available at http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article.htm). these guidelines provided recommended best practices for the diagnosis and treatment of persons with naturally occurring or bioterrorism-related anthrax ...201526632963
improvements to a markerless allelic exchange system for bacillus anthracis.a system was previously developed for conducting i-scei-mediated allelic exchange in bacillus anthracis. in this system, recombinational loss of a chromosomally-integrated allelic exchange vector is stimulated by creation of a double-stranded break within the vector by the homing endonuclease i-scei. although this system is reasonably efficient and represents an improvement in the tools available for allelic exchange in b. anthracis, researchers are nonetheless required to "pick and patch" colon ...201526624016
[selection of disposable personal protective equipment for work with samples containing highly pathogenic microorganisms].emerging microbiological threats, such as sars, ebola, mers-cov, anthrax, cause necessity of considering how effectively protect laboratory workers against dangerous pathogens which might be present in clinical samples. the article presents requirements for personal protective equipment (ppe) in microbiological laboratories and examples of selection and application of disposable ppe.201526591666
effect of particulate adjuvant on the anthrax protective antigen dose required for effective nasal vaccination.successful vaccine development is dependent on the development of effective adjuvants since the poor immunogenicity of modern subunit vaccines typically requires the use of potent adjuvants and high antigen doses. in recent years, adjuvant formulations combining both immunopotentiators and delivery systems have emerged as a promising strategy to develop effective and improved vaccines. in this study we investigate if the association of the mast cell activating adjuvant compound 48/80 (c48/80) wi ...201526087299
anthrax lethal toxin suppresses high glucose induced vegf over secretion through a post-translational mechanism.to prove anthrax lethal toxin (letx) blocks the mitogen activated protein kinases (mapks) activation by degrading the mapk/erk kinases (meks) to suppress vascular endothelial growth factor (vegf) secretion.201526085990
bacillus anthracis spores germinate extracellularly at air-liquid interface in an in vitro lung model under serum-free conditions.to better understand the parameters that govern spore dissemination after lung exposure using in vitro cell systems.201526075586
natural cutaneous anthrax infection, but not vaccination, induces a cd4(+) t cell response involving diverse cytokines.whilst there have been a number of insights into the subsets of cd4(+) t cells induced by pathogenic bacillus anthracis infections in animal models, how these findings relate to responses generated in naturally infected and vaccinated humans has yet to be fully established. we describe the cytokine profile produced in response to t cell stimulation with a previously defined immunodominant antigen of anthrax, lethal factor (lf), domain iv, in cohorts of individuals with a history of cutaneous ant ...201526075052
bridging non-human primate correlates of protection to reassess the anthrax vaccine adsorbed booster schedule in humans.anthrax vaccine adsorbed (ava, biothrax) is approved for use in humans as a priming series of 3 intramuscular (i.m.) injections (0, 1, 6 months; 3-im) with boosters at 12 and 18 months, and annually thereafter for those at continued risk of infection. a reduction in ava booster frequency would lessen the burden of vaccination, reduce the cumulative frequency of vaccine associated adverse events and potentially expand vaccine coverage by requiring fewer doses per schedule. because human inhalatio ...201526072016
anthrax lethal toxin-induced lung injury and treatment by activating mk2.anthrax is associated with severe vascular leak, which is caused by the bacterial lethal toxin (letx). pleural effusions and pulmonary edema that occur in anthrax are believed to reflect endothelial injury caused by the anthrax toxin. since vascular leak can also be observed consistently in rats injected intravenously with letx, the latter might present a simple physiologically relevant animal model of acute lung injury (ali). such a model could be utilized in evaluating and developing better tr ...201526066827
inhibitor bound crystal structures of bacterial nitric oxide synthase.nitric oxide generated by bacterial nitric oxide synthase (nos) increases the susceptibility of gram-positive pathogens staphylococcus aureus and bacillus anthracis to oxidative stress, including antibiotic-induced oxidative stress. not surprisingly, nos inhibitors also improve the effectiveness of antimicrobials. development of potent and selective bacterial nos inhibitors is complicated by the high active site sequence and structural conservation shared with the mammalian nos isoforms. to expl ...201526062720
curing both virulent mega-plasmids from bacillus anthracis wild-type strain a16 simultaneously using plasmid incompatibility.plasmid-cured derivative strains of bacillus anthracis are frequently used in laboratory studies. plasmid incompatibility, which does not increase the risk of chromosomal mutation, is a useful method for plasmid curing. however, in bacteria containing multiple plasmids, it often requires the sequential introduction of multiple, specific incompatibility plasmids. this lengthy process renders the traditional plasmid incompatibility method inefficient and mutation-prone. in this study, we successfu ...201526059513
analysis of pregnancy and infant health outcomes among women in the national smallpox vaccine in pregnancy registry who received anthrax vaccine adsorbed.the national smallpox vaccine in pregnancy registry (nsvipr) actively follows women inadvertently vaccinated with smallpox vaccine during or shortly before pregnancy to evaluate their reproductive health outcomes. approximately 65% of nsvipr participants also inadvertently received anthrax vaccine adsorbed (ava) while pregnant, providing a ready opportunity to evaluate pregnancy and infant health outcomes among these women. ava-exposed pregnancies were ascertained using nsvipr and electronic hea ...201526049005
loss of homogentisate 1,2-dioxygenase activity in bacillus anthracis results in accumulation of protective pigment.melanin production is important to the pathogenicity and survival of some bacterial pathogens. in bacillus anthracis, loss of hmga, encoding homogentisate 1,2-dioxygenase, results in accumulation of a melanin-like pigment called pyomelanin. pyomelanin is produced in the mutant as a byproduct of disrupted catabolism of l-tyrosine and l-phenylalanine. accumulation of pyomelanin protects b. anthracis cells from uv damage but not from oxidative damage. neither loss of hmga nor accumulation of pyomel ...201526047497
pharmaceutical approval update.ivabradine (corlanor) for heart failure, anthrax immune globulin intravenous (human) (anthrasil) for inhalational anthrax, and glatiramer acetate (glatopa) for relapsing forms of multiple sclerosis.201526045644
monitoring biothreat agents (francisella tularensis, bacillus anthracis and yersinia pestis) with a portable real-time pcr instrument.in the event of suspected releases or natural outbreaks of contagious pathogens, rapid identification of the infectious agent is essential for appropriate medical intervention and disease containment. the purpose of this study was to compare the performance of a novel portable real-time pcr thermocycler, pikoreal™, to the standard real-time pcr thermocycler, applied biosystems® 7300 (abi 7300), for the detection of three high-risk biothreat bacterial pathogens: francisella tularensis, bacillus a ...201526043838
bacillus anthracis capsular conjugates elicit chimpanzee polyclonal antibodies that protect mice from pulmonary anthrax.the immunogenicity of bacillus anthracis capsule (poly-γ-d-glutamic acid [pga]) conjugated to recombinant b. anthracis protective antigen (rpa) or to tetanus toxoid (tt) was evaluated in two anthrax-naive juvenile chimpanzees. in a previous study of these conjugates, highly protective monoclonal antibodies (mabs) against pga were generated. this study examines the polyclonal antibody response of the same animals. preimmune antibodies to pga with titers of >10(3) were detected in the chimpanzees. ...201526041039
the worldwide distribution of genetically and phylogenetically diverse bacillus cereus isolates harbouring bacillus anthracis-like plasmids.bacillus cereus is a close relative of b. anthracis, the causative agent of anthrax whose pathogenic determinants are located on pxo1 and pxo2 plasmids. bacillus anthracis-like plasmids have been also noted among b. cereus, however, genetic features of b. cereus harbouring these elements remain largely undescribed, especially from the global perspective. herein, we present the genetic polymorphism, population structure and phylogeny of b. cereus with pxo1-/pxo2-like plasmids originating from arg ...201526033739
bacillus anthracis meningitis during an outbreak of injectional anthrax, scotland, uk. 201526033672
esxb, a secreted protein from bacillus anthracis forms two distinct helical bundles.the esxb protein from bacillus anthracis belongs to the wxg100 family, a group of proteins secreted by a specialized secretion system. we have determined the crystal structures of recombinant esxb and discovered that the small protein (∼10 kda), comprised of a helix-loop-helix (hlh) hairpin, is capable of associating into two different helical bundles. the two basic quaternary assemblies of esxb are an antiparallel (ap) dimer and a rarely observed bisecting u (bu) dimer. this structural duality ...201526032645
[the epidemiological situation in the republic of abkhazia in 2013-2014 and rospotrebnadzor participation in activities for its stabilization].official statistics of republican ses on infectious diseases are used. the characteristics of the current epidemiological situation in the republic of abkhazia is given. the analysis of infectious dis- eases from 2012 to 2014 is presented. it was found that the most widespread infectious diseases are acute respiratory viral and acute intestinal infection. during the analyzed period in the country outbreaks of dysentery, whooping cough and measles were reported. epidemic threat is the presence of ...201526016353
micropatterned macrophage analysis reveals global cytoskeleton constraints induced by bacillus anthracis edema toxin.bacillus anthracis secretes the edema toxin (et) that disrupts the cellular physiology of endothelial and immune cells, ultimately affecting the adherens junction integrity of blood vessels that in turn leads to edema. the effects of et on the cytoskeleton, which is critical in cell physiology, have not been described thus far on macrophages. in this study, we have developed different adhesive micropatterned surfaces (l and crossbow) to control the shape of bone marrow-derived macrophages (bmdms ...201526015478
identification of potent and compartment-selective small molecule furin inhibitors using cell-based assays.the proprotein convertase furin is implicated in a variety of pathogenic processes such as bacterial toxin activation, viral propagation, and cancer. several groups have identified non-peptide compounds with high inhibitory potency against furin in vitro, although their efficacy in various cell-based assays is largely unknown. in this study we show that certain guanidinylated 2,5-dideoxystreptamine derivatives exhibit interesting ex vivo properties. compound 1b (1,1'-(4-((2,4-diguanidino-5-(4-gu ...201526003844
the function of plcr in bacillus anthracis vaccine strain a16r.bacillus anthracis, b. thuringiensis and b. cereus are members of the b. cereus group. they share high genetic similarity. whereas plcr (phospholipase c regulator) usually encodes a functional pleiotropic activator protein in b. cereus and b. thuringiensis isolates, a characteristic nonsense mutation is found in all b. anthracis strains investigated, making the gene dysfunctional. to study the function of plcr in b. anthracis, we used the b. cereus cmcc63301 genome as a template and constructed ...201525998439
advances in anthrax detection: overview of bioprobes and biosensors.anthrax is an infectious disease caused by bacillus anthracis. although anthrax commonly affects domestic and wild animals, it causes a rare but lethal infection in humans. a variety of techniques have been introduced and evaluated to detect anthrax using cultures, polymerase chain reaction, and immunoassays to address the potential threat of anthrax being used as a bioweapon. the high-potential harm of anthrax in bioterrorism requires sensitive and specific detection systems that are rapid, fie ...201525987133
an optimized coupled assay for quantifying diaminopimelate decarboxylase activity.diaminopimelate decarboxylase (dapdc) catalyzes the conversion of meso-dap to lysine and carbon dioxide in the final step of the diaminopimelate (dap) pathway in plants and bacteria. given its absence in humans, dapdc is a promising antibacterial target, particularly considering the rise in drug-resistant strains from pathogens such as escherichia coli and mycobacterium tuberculosis. here, we report the optimization of a simple quantitative assay for measuring dapdc catalytic activity using sacc ...201525986217
fast and sensitive detection of an anthrax biomarker using sers-based solenoid microfluidic sensor.we report the application of a fully automated surface-enhanced raman scattering (sers)-based solenoid-embedded microfluidic device to the quantitative and sensitive detection of anthrax biomarker poly-γ-d-glutamic acid (pga) in solution. analysis is based on the competitive reaction between pga and pga-conjugated gold nanoparticles with anti-pga-immobilized magnetic beads within a microfluidic environment. magnetic immunocomplexes are trapped by yoke-type solenoids embedded within the device, a ...201525985198
effects of metalloprotease anthrax lethal factor on its peptide-based inhibitor r9lf-1.the metalloprotease lethal factor (lf) from bacillus anthracis plays a vital role in anthrax toxin action, and thus becomes a target for anti-anthrax therapy. following the guidelines based on existing metalloprotease inhibitors, we designed a 'first-generation' lf inhibitor r9lf-1. this inhibitor was shown to be very stable by itself in a wide range of ph and temperature and able to inhibit lf activity in vitro. however, as we reported previously in the presence of lf, this inhibitor was degrad ...201525981534
reaerosolization of spores from flooring surfaces to assess the risk of dissemination and transmission of infections.the aim of this study was to quantify reaerosolization of microorganisms caused by walking on contaminated flooring to assess the risk to individuals accessing areas contaminated with pathogenic organisms, for example, spores of bacillus anthracis. industrial carpet and polyvinyl chloride (pvc) floor coverings were contaminated with aerosolized spores of bacillus atrophaeus by using an artist airbrush to produce deposition of ∼10(3) to 10(4) cfu · cm(-2). microbiological air samplers were used t ...201525979883
a review of back-calculation techniques and their potential to inform mitigation strategies with application to non-transmissible acute infectious diseases.back-calculation is a process whereby generally unobservable features of an event leading to a disease outbreak can be inferred either in real-time or shortly after the end of the outbreak. these features might include the time when persons were exposed and the source of the outbreak. such inferences are important as they can help to guide the targeting of mitigation strategies and to evaluate the potential effectiveness of such strategies. this article reviews the process of back-calculation wi ...201525977955
novel furin inhibitors with potent anti-infectious activity.new peptidomimetic furin inhibitors with unnatural amino acid residues in the p3 position were synthesized. the most potent compound 4-guanidinomethyl-phenylacteyl-arg-tle-arg-4-amidinobenzylamide (mi-1148) inhibits furin with a ki value of 5.5 pm. the derivatives also strongly inhibit pc1/3, whereas pc2 is less affected. selected inhibitors were tested in cell culture for antibacterial and antiviral activity against infectious agents known to be dependent on furin activity. a significant protec ...201525974265
[general procedures in response to suspected attacks with highly contagious and pathogenic agents].the discovery of undefined powders that are content of letters or parcels with or without threats in writing addressed to institutions, groups or persons, often raises the suspicion of an attack involving biological agents such as anthrax. subsequent investigations and analyses by local authorities often aim at excluding anthrax or anthrax spores. suspicion and actions are then mistakenly justified by referring to the 2001 anthrax letter attacks in the usa, which now lie more than 10 years in th ...201525963640
lytic enzyme-assisted germination of bacillus anthracis and bacillus subtilis spores.the goal of this work was to determine conditions under which external application of a spore germination-specific lytic enzyme (gsle) can increase the germination efficiency of spore populations.201525963559
updating a b. anthracis risk model with field data from a bioterrorism incident.in this study, a bayesian framework was applied to update a model of pathogen fate and transport in the indoor environment. distributions for model parameters (e.g., release quantity of b. anthracis spores, risk of illness, spore setting velocity, resuspension rate, sample recovery efficiency, etc.) were updated by comparing model predictions with measurements of b. anthracis spores made after one of the 2001 anthrax letter attacks. the updating process, which was implemented by using markov cha ...201525961107
diagnostic performance characteristics of a rapid field test for anthrax in cattle.although diagnosis of anthrax can be made in the field with a peripheral blood smear, and in the laboratory with bacterial culture or molecular based tests, these tests require either considerable experience or specialised equipment. here we report on the evaluation of the diagnostic sensitivity and specificity of a simple and rapid in-field diagnostic test for anthrax, the anthrax immunochromatographic test (aict). the aict detects the protective antigen (pa) component of the anthrax toxin pres ...201525956134
surrogate testing suggests that chlorine dioxide gas exposure would not inactivate ebola virus contained in environmental blood contamination.the ability to decontaminate a room potentially containing the ebola virus is important to healthcare facilities in the united states. ebola virus remains viable in body fluids, a room that has housed a patient with ebola virus disease must have all surfaces manually wiped with an approved disinfectant, which increases occupational exposure risk. this study evaluated the efficacy of gaseous chlorine dioxide inactivation of bacterial organisms in blood as ebola virus surrogates and as the organis ...201525955403
rapid detection of bacillus anthracis in complex food matrices using phage-mediated bioluminescence.bacillus anthracis, the causative agent of anthrax, is considered a high-priority agent that may be used in a food-related terrorist attack because it can be contracted by ingestion and it also forms spores with heat and chemical resistance. thus, novel surveillance methodologies to detect b. anthracis on adulterated foods are important for bioterrorism preparedness. we describe the development of a phage-based bioluminescence assay for the detection of b. anthracis on deliberately contaminated ...201525951391
capture of methyl bromide emissions with activated carbon following the fumigation of a small building contaminated with a bacillus anthracis spore simulant.a wide-area bacillus anthracis spore contamination incident will present immense challenges related to decontamination capacity. for this reason, fumigation with methyl bromide (mebr) has been proposed as a potential remediation option. although a few bench-scale laboratory studies have been conducted to evaluate activated carbon for the capture of mebr, these studies were conducted at conditions replicating commodity fumigation using relatively low mebr concentrations, temperatures, and/or rela ...201525947050
risk-based decision making for reoccupation of contaminated areas following a wide-area anthrax release.this article presents an analysis of postattack response strategies to mitigate the risks of reoccupying contaminated areas following a release of bacillus anthracis spores (the bacterium responsible for causing anthrax) in an urban setting. the analysis is based on a hypothetical attack scenario in which individuals are exposed to b. anthracis spores during an initial aerosol release and then placed on prophylactic antibiotics that successfully protect them against the initial aerosol exposure. ...201525946233
immunoassay for capsular antigen of bacillus anthracis enables rapid diagnosis in a rabbit model of inhalational anthrax.inhalational anthrax is a serious biothreat. effective antibiotic treatment of inhalational anthrax requires early diagnosis; the further the disease has progressed, the less the likelihood for cure. current means for diagnosis such as blood culture require several days to a result and require advanced laboratory infrastructure. an alternative approach to diagnosis is detection of a bacillus anthracis antigen that is shed into blood and can be detected by rapid immunoassay. the goal of the study ...201525942409
biochemical and structural analysis of an eis family aminoglycoside acetyltransferase from bacillus anthracis.proteins from the enhanced intracellular survival (eis) family are versatile acetyltransferases that acetylate amines at multiple positions of several aminoglycosides (ags). their upregulation confers drug resistance. homologues of eis are present in diverse bacteria, including many pathogens. eis from mycobacterium tuberculosis (eis_mtb) has been well characterized. in this study, we explored the ag specificity and catalytic efficiency of the eis family protein from bacillus anthracis (eis_ban) ...201525928210
an overview of investigational toxin-directed therapies for the adjunctive management of bacillus anthracis infection and sepsis.sepsis with bacillus anthracis infection has a very high mortality rate despite appropriate antibiotic and supportive therapies. over the past 15 years, recent outbreaks in the us and in europe, coupled with anthrax's bioterrorism weapon potential, have stimulated efforts to develop adjunctive therapies to improve clinical outcomes. since lethal toxin and edema toxin (lt and et) make central contributions to the pathogenesis of b. anthracis, these have been major targets in this effort.201525920540
a case of fatal gastrointestinal anthrax in north eastern iran.background. bacillus species are aerobic or facultative anaerobic, gram-positive, or gram-variable spore-forming rods. they are ubiquitous in the environmental sources. bacillus anthracis may usually cause three forms of anthrax: inhalation, gastrointestinal, and cutaneous. the gastrointestinal (gi) anthrax develops after eating contaminated meat. in this paper we report septic intestinal anthrax. case presentation. we report an isolation of bacillus anthracis from blood culture of patient with ...201525918652
bcla and toxin antigens augment each other to protect nmri mice from lethal bacillus anthracis challenge.while proving highly effective in controlling anthrax in farm animals all over the world currently attenuated live anthrax vaccines employed in a veterinary context suffer from drawbacks such as residual virulence, short term protection, variation in quality and, most importantly, lack of efficacy if administered simultaneously with antibiotics. these limitations have stimulated the development of non-living component vaccines which induce a broad spectrum immune response capable of targeting bo ...201525917676
the neglected zoonoses--the case for integrated control and advocacy.the neglected zoonotic diseases (nzds) have been all but eradicated in wealthier countries, but remain major causes of ill-health and mortality across africa, asia, and latin america. this neglect is, in part, a consequence of under-reporting, resulting in an underestimation of their global burden that downgrades their relevance to policy-makers and funding agencies. increasing awareness about the causes of nzds and how they can be prevented could reduce the incidence of many endemic zoonoses. a ...201525911990
acquired coagulant factor viii deficiency induced by bacillus anthracis lethal toxin in mice.mice treated with anthrax lethal toxin (lt) exhibit hemorrhage caused by unknown mechanisms. moreover, lt treatment in mice induced liver damage. in this study, we hypothesized that a suppressed coagulation function may be associated with liver damage, because the liver is the major producing source of coagulation factors. the hepatic expression of coagulant factors and the survival rates were analyzed after cultured cells or mice were exposed to lt. in agreement with our hypothesis, lt induces ...201525906166
evaluation of new dihydrophthalazine-appended 2,4-diaminopyrimidines against bacillus anthracis: improved syntheses using a new pincer complex.the synthesis and evaluation of ten new dihydrophthalazine-appended 2,4-diaminopyrimidines as potential drugs to treat bacillus anthracis is reported. an improved synthesis utilizing a new pincer catalyst, dichlorobis[1-(dicyclohexylphosphanyl)-piperidine]palladium(ii), allows the final heck coupling to be performed at 90 °c using triethylamine as the base. these milder conditions have been used to achieve improved yields for new and previously reported substrates with functional groups that deg ...201525905602
survey of uk health care first responders' knowledge of personal protective equipment requirements.an adequate level of personal protective equipment (ppe) is necessary when treating patients with highly infectious diseases or those contaminated with hazardous substances.201525901721
[molecular model of anthrax toxin translocation into target-cells].anthrax toxin is formed from three components: protective antigen (pa), lethal (lf) and edema (ef) factors. pa83 is cleaved by cell surface protease furin to produce a 63-kda fragment (pa63). pa63 and lf/ef molecules are assembled to anthrax toxin complexes: oligomer pa63 x 7 + lf/ef x 3. assembly is occurred during of binding with cellular receptor or near surface of target-cell. this toxin complex forms pore and induces receptor-mediated endocytosis. formed endosome consists extracellular liqu ...201525898749
tertiary amides of salinomycin: a new group of antibacterial agents against bacillus anthracis and methicillin-resistant staphylococcus epidermidis.for the first time, a series of tertiary amides of polyether antibiotic-salinomycin have been obtained and screened for their antibacterial activity against different strains of bacteria, including bacillus anthracis and clinical methicillin-resistant staphylococcus epidermidis (mrse). moreover, biofilm inhibition of mrse and genotoxicity tests against bacillus subtilis have been performed. our studies show that salinomycin and its some derivatives are active against tested bacteria and exhibite ...201525891104
genetic characterization of bacillus anthracis in guizhou province, southwest of china.bacillus (b.) anthracis is the pathogen that causes fatal anthrax. guizhou province is an old foci of anthrax in the southwest of china. human anthrax has also been frequently reported in guizhou in recent year. however, there is limited information on the genetic background of local b. anthracis isolates in guizhou province. strain-specific detection of this bacterium using molecular approaches has enhanced our knowledge of microbial genetics. in the present study, we employed multiple locus va ...201525887647
the nlrp1 inflammasomes.inflammasomes are cytosolic protein complexes that serve as platforms for the recruitment and activation of the pro-inflammatory caspase-1 protease. caspase-1 activation leads to processing and maturation of the cytokines interleukin-1β and interleukin-18 and a lytic form of cell death termed pyroptosis. inflammasome assembly is initiated by cytosolic sensors in response to microbial infections. many of these sensors, including nlrp1 (nlr family, pyrin domain containing 1), are described to form ...201525879281
[development and comparative evaluation of up-converting phosphor technology based lateral flow assay for rapid detection of yersinia pestis, bacillus anthracis spore and brucella spp].to develop an up-converting phosphor technology based lateral flow (upt-lf) assay for rapid and quantitative detection of yersinia pestis, bacillus anthracis spore and brucella spp.and make the comparison with biothreat alert (bta) test strips (tetracore inc., usa).201525876487
diverse supramolecular structures formed by self-assembling proteins of the bacillus subtilis spore coat.bacterial spores (endospores), such as those of the pathogens clostridium difficile and bacillus anthracis, are uniquely stable cell forms, highly resistant to harsh environmental insults. bacillus subtilis is the best studied spore-former and we have used it to address the question of how the spore coat is assembled from multiple components to form a robust, protective superstructure. b. subtilis coat proteins (coty, cote, cotv and cotw) expressed in escherichia coli can arrange intracellularly ...201525872412
deltonin induced both apoptosis and autophagy in head and neck squamous carcinoma fadu cell.for decades, despite the advancement of medical science, the prognosis of head and neck squamous cell carcinoma (hnscc), has not improved. deltonin is one of the major active components of dioscorea zingiberensis wright that has been used for anthrax, rheumatic heart disease, rheumatoid arthritis etc. by employing hnscc fadu cell and normal human epidermal keratinocyte, we investigate deltonin efficacy and associated mechanism in both cell culture and nude mice xenografts. deltonin treatment sel ...201525866222
regulation and rna-binding properties of hfq-like rna chaperones in bacillus anthracis.small rnas (srnas) are important modulators of gene expression in bacteria. regulation by srnas is yet to be established in bacillus anthracis. here, regulation and rna-binding properties of hfq-like rna chaperones in b. anthracis are investigated.201525863287
bacillus anthracis edema but not lethal toxin challenge in rats is associated with depressed myocardial function in hearts isolated and tested in a langendorff system.although direct myocardial depression has been implicated in the lethal effects of bacillus anthracis lethal toxin (lt), in hearts isolated from healthy rats and perfused under constant pressure, neither lt or edema toxin (et) in typically lethal concentrations depressed myocardial function. in the present study, we challenged rats with lt and et and performed in vivo and ex vivo heart measures. sprague-dawley rats infused over 24 h with lt (n = 94), et (n = 99), or diluent (controls; n = 50) we ...201525862834
recent developments in understanding the iron acquisition strategies of gram positive pathogens.iron is a versatile redox-active catalyst and a required cofactor within a diverse array of biological processes. to almost all organisms, iron is both essential and potentially toxic, where homeostatic concentrations must be stringently maintained. within the iron-restricted host, the survival and proliferation of microbial invaders is contingent upon exploiting the host iron pool. bacteria express a multitude of complex, and often redundant means of acquiring iron, including surface-associated ...201525862688
biosensors for monitoring airborne pathogens.airborne pathogens affect both humans and animals and are often highly and rapidly transmittable. many problematic airborne pathogens, both viral (influenza a/h1n1, rubella, and avian influenza/h5n1) and bacterial (mycobacterium tuberculosis, streptococcus pneumoniae, and bacillus anthracis), have huge impacts on health care and agricultural applications, and can potentially be used as bioterrorism agents. many different laboratory-based methods have been introduced and are currently being used. ...201525862683
using light scattering to determine the stoichiometry of protein complexes.the stoichiometry of a protein complex can be calculated from an accurate measurement of the complex's molecular weight. multiangle laser light scattering in combination with size exclusion chromatography and interferometric refractometry provides a powerful means for determining the molecular weights of proteins and protein complexes. in contrast to conventional size exclusion chromatography and analytical centrifugation, measurements do not rely on the use of molecular weight standards and are ...201525859953
chemical feasibility of the general acid/base mechanism of glms ribozyme self-cleavage.in numerous gram-positive bacteria, the glms ribozyme or catalytic riboswitch regulates the expression of glucosamine-6-phosphate (glcn6p) synthase via site-specific cleavage of its sugar-phosphate backbone in response to glcn6p ligand binding. biochemical data have suggested a crucial catalytic role for an active site guanine (g40 in thermoanaerobacter tengcongensis, g33 in bacillus anthracis). we used hybrid quantum chemical/molecular mechanical (qm/mm) calculations to probe the mechanism wher ...201525858644
human anthrax as a re-emerging disease.anthrax is primarily a disease of herbivores and the etiological agent is b. anthracis which is a gram-positive, aerobic, spore-forming, and rod shaped bacterium. bacillus anthracis spores are highly resistant to heat, pressure, ultraviolet and ionizing radiation, chemical agents and disinfectants. for these reasons, b. anthracis spores are an attractive choice as biological agents for the use of bioweapon and/or bioterrorism. soil is the main reservoir for the infectious agent. the disease most ...201525851429
evaluation of anthrax vaccine safety in 18 to 20 year olds: a first step towards age de-escalation studies in adolescents.anthrax vaccine adsorbed (ava, biothrax(®)) is recommended for post-exposure prophylaxis administration for the us population in response to large-scale bacillus anthracis spore exposure. however, no information exists on ava use in children and ethical barriers exist to performing pre-event pediatric ava studies. a presidential ethics commission proposed a potential pathway for such studies utilizing an age de-escalation process comparing safety and immunogenicity data from 18 to 20 year-olds t ...201525850022
protein composition of the outermost exosporium-like layer of clostridium difficile 630 spores.clostridium difficile spores are considered the morphotype of infection, transmission and persistence of c. difficile infections. there is a lack of information on the composition of the outermost exosporium layer of c. difficile spores. using recently developed exosporium removal methods combined with ms/ms, we have established a gel-free approach to analyze the proteome of the exosporium of c. difficile spores of strain 630. a total of 184 proteins were found in the exosporium layer of c. diff ...201525849250
biosynthesis, characterization, and antimicrobial applications of silver nanoparticles.in the present study, the strain brevibacterium frigoritolerans dc2 was explored for the efficient and extracellular synthesis of silver nanoparticles. these biosynthesized silver nanoparticles were characterized by ultraviolet-visible spectrophotometry, which detected the formation of silver nanoparticles in the reaction mixture and showed a maximum absorbance at 420 nm. in addition, field emission transmission electron microscopy revealed the spherical shape of the nanoparticles. the dynamic l ...201525848272
molecular diversity of bacillus anthracis in the netherlands: investigating the relationship to the worldwide population using whole-genome snp discovery.bacillus anthracis, the causative agent of anthrax, has been widely described as a clonal species. here we report the use of both canonical snp analysis and whole-genome sequencing to characterize the phylogenetic lineages of b. anthracis from the netherlands. eleven strains isolated over a 25-years period (1968-1993) were paired-end sequenced using parallel sequencing technology. five cansnp groups or lineages, i.e. a.br.001/002 (n=6), a.br.aust94 (n=2), a.br.008/011 (n=1), a.br.011/009 (n=1) a ...201525843650
[characteristics of isogenic variants of bacillus anthracis with various content of virulence plasmids].production and characteristics by main cultural-morphologic and antigenic properties of isogenic variants bacillus anthracis, that differ by the presence of virulence plasmids.201525842948
development of receptor-based inhibitory rna aptamers for anthrax toxin neutralization.anthrax toxin excreted by bacillus anthracis is the key causative agent of infectious anthrax disease. in the present study, we targeted the binding of pa to the atr/tem8 von willebrand factor type a (vwa) domain, which we cloned into escherichia coli and purified to homogeneity under denaturing conditions. to develop an anthrax toxin inhibitor, we selected and identified short single strand rna aptamers (approximately 30mer) consisting of different sequences of nucleic acids with a high binding ...201525841381
the angiopoietin-tie2 signaling axis in the vascular leakage of systemic inflammation.the ability of small blood vessels to undergo rapid, reversible morphological changes is essential for the adaptive response to tissue injury or local infection. a canonical feature of this response is transient hyperpermeability. however, when leakiness is profound or persistent, adverse consequences accrue to the host, including organ dysfunction and shock. a growing body of literature identifies the tie2 receptor, a transmembrane tyrosine kinase highly enriched in the endothelium, as an impor ...201525838975
anthrax in injecting drug users: the need for increased vigilance in the clinic.the emergence of a previously unrecognized route of bacillus anthracis infection over the last few years has led to concern: sporadic anthrax outbreaks among heroin users in northern europe have demonstrated the severe pathology associated with the newly described 'injectional anthrax'. with a high case fatality rate and non-specific early symptoms, this is a novel clinical manifestation of an old disease. lack of awareness of this syndrome among emergency room clinicians can lead to a delayed d ...201525831413
capsules, toxins and atxa as virulence factors of emerging bacillus cereus biovar anthracis.emerging b. cereus strains that cause anthrax-like disease have been isolated in cameroon (ca strain) and côte d'ivoire (ci strain). these strains are unusual, because their genomic characterisation shows that they belong to the b. cereus species, although they harbour two plasmids, pbcxo1 and pbcxo2, that are highly similar to the pxo1 and pxo2 plasmids of b. anthracis that encode the toxins and the polyglutamate capsule respectively. the virulence factors implicated in the pathogenicity of the ...201525830379
anthrax vaccine associated deaths in miniature horses.during a widespread anthrax outbreak in canada, miniature horses were vaccinated using a live spore anthrax vaccine. several of these horses died from an apparent immune-mediated vasculitis temporally associated with this vaccination. during the course of the outbreak, other miniature horses from different regions with a similar vaccination history, clinical signs, and necropsy findings were found.201525829553
two putative polysaccharide deacetylases are required for osmotic stability and cell shape maintenance in bacillus anthracis.membrane-anchored lipoproteins have a broad range of functions and play key roles in several cellular processes in gram-positive bacteria. ba0330 and ba0331 are the only lipoproteins among the 11 known or putative polysaccharide deacetylases of bacillus anthracis. we found that both lipoproteins exhibit unique characteristics. ba0330 and ba0331 interact with peptidoglycan, and ba0330 is important for the adaptation of the bacterium to grow in the presence of a high concentration of salt, whereas ...201525825488
first autochthonous coinfected anthrax in an immunocompetent patient.cutaneous anthrax has a mortality rate of 20% if no antibacterial treatment is applied. the clinical manifestations of cutaneous anthrax are obviously striking, but coinfection may produce atypical lesions and mask the clinical manifestations and proper laboratory diagnosis. anthrax is known to be more common in the middle east and iran is one of the countries in which the zoonotic form of anthrax may still be encountered. we report a case of a 19-years-old male who used to apply venetian ceruse ...201526451148
accelerating the smith-waterman algorithm with interpair pruning and band optimization for the all-pairs comparison of base sequences.the smith-waterman algorithm is known to be a more sensitive approach than heuristic algorithms for local sequence alignment algorithms. despite its sensitivity, a greater time complexity associated with the smith-waterman algorithm prevents its application to the all-pairs comparisons of base sequences, which aids in the construction of accurate phylogenetic trees. the aim of this study is to achieve greater acceleration using the smith-waterman algorithm (by realizing interpair block pruning a ...201526445214
anthrax prophylaxis: recent advances and future directions.anthrax is a serious, potentially fatal disease that can present in four distinct clinical patterns depending on the route of infection (cutaneous, gastrointestinal, pneumonic, or injectional); effective strategies for prophylaxis and therapy are therefore required. this review addresses the complex mechanisms of pathogenesis employed by the bacterium and describes how, as understanding of these has developed over many years, so too have current strategies for vaccination and therapy. it covers ...201526441934
global metabolomic analysis of a mammalian host infected with bacillus anthracis.whereas dna provides the information to design life and proteins provide the materials to construct it, the metabolome can be viewed as the physiology that powers it. as such, metabolomics, the field charged with the study of the dynamic small-molecule fluctuations that occur in response to changing biology, is now being used to study the basis of disease. here, we describe a comprehensive metabolomic analysis of a systemic bacterial infection using bacillus anthracis, the etiological agent of a ...201526438791
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